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Cutting Edge: Stimulation with the Cognate Self-Antigen Induces Expression of the Ly49A Receptor on Self-Reactive T Cells Which Modulates Their Responsiveness ¹

Leslie Saurer^2,*, Inge Seibold^*, Claudio Vallan^*, Werner Held and Christoph Mueller^3,*

^* Institute of Pathology, Division of Immunopathology, University of Bern, Bern, Switzerland; and Ludwig Institute of Cancer Research, University of Lausanne, Lausanne, Switzerland

NK cell self-tolerance is maintained by inhibitory receptors specific for MHC class I molecules. Inhibitory NK receptors are also expressed on memory CD8 T cells but their biological relevance on T cells is unclear. In this study, we describe the expression of the Ly49A receptor on a subset of autoreactive T cells which persist in mice double-transgenic for the lymphocytic choriomeningitis virus-derived peptide gp33 and a TCR specific for the gp33. No Ly49A-expressing cells are found in TCR single-transgenic mice, indicating that the presence of the autoantigen is required for Ly49A induction. Direct evidence for an Ag-specific initiation of Ly49A expression has been obtained in vitro after stimulation of autoreactive TCR T cells with the cognate self-Ag. This expression of Ly49A substantially reduces Ag-specific activation of autoreactive T cells. These findings thus suggest that autoantigen-specific induction of inhibitory NK cell receptors on T cells may contribute to peripheral self-tolerance.

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